Computed tomography (CT) has become a mainstay in diagnostic imaging. The high clinical impact of CT has led to rapidly increased utilization and, at the same time, public concerns about the potential risk to patients. Although many technologies have been developed to reduce radiation dose from CT, significant additional improvements are needed to minimize radiation dose without compromising diagnostic performance. In this U01 project, the interdisciplinary team will develop dose-saving technologies for three key CT imaging chain components and demonstrate their clinical benefits by systematic integration and evaluation. Specifically, the three components comprise (1) a fully dynamic x-ray source that adaptively modulates the radiation incident on a patient; (2) an energy-discriminating photon-counting x-ray detector with small detector pitch, high count-rate, and five energy windows; and (3) an advanced low-dose spectral reconstruction methods in a compressive sensing and statistical reconstruction framework. The proposed source, detector and reconstruction technologies are highly synergistic. These technologies will be integrated into a CT test-bed system to provide high dose efficiency permitting sub-mSv CT scans for common diagnostic procedures, fine spatial resolution nearly doubling what is provided by the state-of-the-art commercial CT scanners, and equally important, spectral imaging capabilities to facilitate or enable material characterization and other applications. The performance of the proposed CT test-bed will be thoroughly investigated in numerical simulation, and validated with physical and ex vivo experiments. The characterized performance will set the stage for the development of future clinical CT scanners. Because the novel technologies developed in this project are compatible with 3rd generation fan-beam/multi-slice CT system geometries, it would be relatively easy for manufacturers to translate them into products for broad clinical use. If the aims of the U01 project are realized, the benefits to the radiological community will be dramatic: general-purpose CT imaging at radiation dose less than 1 mSv, the largest improvement in CT spatial resolution in over 30 years, and powerful spectral CT imaging capabilities with numerous opportunities.